Table of Contents

Research Focus for Clinicians

A systematic review was undertaken to summarize the evidence regarding the efficacy, comparative effectiveness, and safety of subcutaneous and sublingual immunotherapy for adult and pediatric patients. All included studies are randomized controlled trials (RCTs) and were published from January 1967 to May 2012. There are 74 RCTs on the efficacy and safety of subcutaneous immunotherapy (SCIT), 60 RCTs on the efficacy and safety of sublingual immunotherapy (SLIT), and 8 RCTs on head-to-head comparisons between both forms of immunotherapy. This summary is provided to assist clinicians in decisionmaking along with a patient’s values and preferences. Reviews of evidence should not be construed to represent clinical recommendations or guidelines. The full report can be accessed on the right side of this Web page.

Background

The medical management of patients with allergic rhinitis and allergic asthma includes allergen avoidance, pharmacotherapy, and immunotherapy. Daily use of pharmacotherapies for allergic rhinitis symptoms raises issues related to adherence, safety, and cost. Long-term use of inhaled steroids, long-acting bronchodilators, and leukotriene antagonists for asthma control have risks for moderate to severe adverse effects.

Allergen immunotherapy is typically used for patients whose allergic rhinoconjunctivitis and allergic asthma symptoms cannot be controlled by medication and environmental control, patients who cannot tolerate their medications, or patients who do not comply with chronic medication regimens. The U.S. Food and Drug Administration (FDA) has approved the use of allergen extracts for SCIT for treating allergic rhinitis and allergic asthma.

In the United States, a patient with allergies undergoing immunotherapy receives subcutaneous injections—in increasing doses—of an allergen-containing extract comprised of the relevant allergens to which he or she is sensitive in an attempt to suppress or eliminate allergy-related symptoms. There is considerable interest in using similar allergen extracts as SLIT as an alternative to SCIT. In the included studies, SLIT specifically refers to allergen extracts administered sublingually in the form of drops. Studies on sublingual tablets are not included here. Allergen extract drops are placed under the tongue for local absorption to desensitize the allergic individual over a period of months to years and to diminish allergic symptoms. SLIT is not currently FDA approved for use in the United States. However, some physicians are using subcutaneous formulations of allergens off-label for sublingual desensitization in the treatment of allergic respiratory conditions. This is largely based on products that have been researched for several years in the United States and Europe and are approved for use by European regulatory authorities.

Conclusions

There is sufficient evidence to support the overall effectiveness and safety of both SCIT and SLIT for treating allergic rhinoconjunctivitis and asthma (Tables 1 and 2).

However, there is not enough evidence to determine if either SCIT or SLIT is superior.

SCIT and SLIT are usually safe, although local reactions are commonly reported regardless of the mode of delivery (Table 3).

Serious, life-threatening reactions are rare, although they can occur (see SCIT, Table 3). SLIT studies mainly include patients with allergic rhinitis and/or mild asthma. Safety outcomes for SLIT should not be extrapolated to more severely affected patients.

Most studies use a single allergen for immunotherapy (Table 4). It may be difficult to extrapolate these results to the use of multiple-allergen regimens, which are commonly used in clinical practice in the United States.

Due to the wide variety of reported regimens, the target SLIT maintenance dose and the duration of therapy are unclear.

Strength of Evidence Scale

High:
High confidence that the evidence reflects the true effect. Further research is very unlikely to change our confidence in the estimate of effect.

Moderate:
Moderate confidence that the evidence reflects the true effect. Further research may change our confidence in the estimate of effect and may change the estimate.

Low:
Low confidence that the evidence reflects the true effect. Further research is likely to change our confidence in the estimate of effect and is likely to change the estimate.

Insufficient:
Evidence is either unavailable or does not permit a conclusion.

Table 3. Adverse Effects*

Study

Adults

Pediatric Patients

* Not all studies reported adverse effects; due to the lack of a consistent reporting system across studies, a meta-analysis of adverse effects was not possible.
SCIT = subcutaneous immunotherapy; SLIT = sublingual immunotherapy

What To Discuss With Your Patients

The benefits and adverse effects of SCIT or SLIT for them or their child

Any comorbid conditions that they or their child may have that would affect their ability to take SCIT or SLIT

Other prescription or over-the-counter medications they are taking during SCIT or SLIT treatment

What adverse effects to look for and when to call their doctor

How often they should be taking SCIT or SLIT

How long they can expect to take SCIT or SLIT

The costs of SCIT and SLIT

Resource for Patients

Allergy Shots and Allergy Drops for Adults and Children, A Review of the Research is a free companion to this clinician research summary. It can help patients talk with their health care professionals about treatment options. It provides information about:

Allergies in general

How allergies are treated

Allergy shots and allergy drops

Benefits of allergy shots and allergy drops for adults and children

Possible side effects of allergy shots and allergy drops for adults and children

Questions to discuss with their doctor

Source

The information in this summary is based on Allergen-Specific Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and/or Asthma: Comparative Effectiveness Review, Comparative Effectiveness Review No. 111, prepared by the Johns Hopkins University Evidence-based Practice Center under Contract No. 290-2007-10061-I for the Agency for Healthcare Research and Quality, March 2013.

This summary was prepared by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine, Houston, TX. It was written by Andrea Humphries, Ph.D., Masayoshi Takashima, M.D., and Michael Fordis, M.D.